Generation and characterization of monoclonal antibodies against pathologically phosphorylated TDP-43.
Inclusions containing TAR DNA binding protein 43 (TDP-43) are a pathological hallmark of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). One of the disease-specific features of TDP-43 inclusions is the aberrant phosphorylation of TDP-43 at serines 409/410 (pS409/410). Here, we...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0298080&type=printable |
| _version_ | 1797194874335789056 |
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| author | Paula Castellanos Otero Tiffany W Todd Wei Shao Caroline J Jones Kexin Huang Lillian M Daughrity Mei Yue Udit Sheth Tania F Gendron Mercedes Prudencio Björn Oskarsson Dennis W Dickson Leonard Petrucelli Yong-Jie Zhang |
| author_facet | Paula Castellanos Otero Tiffany W Todd Wei Shao Caroline J Jones Kexin Huang Lillian M Daughrity Mei Yue Udit Sheth Tania F Gendron Mercedes Prudencio Björn Oskarsson Dennis W Dickson Leonard Petrucelli Yong-Jie Zhang |
| author_sort | Paula Castellanos Otero |
| collection | DOAJ |
| description | Inclusions containing TAR DNA binding protein 43 (TDP-43) are a pathological hallmark of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). One of the disease-specific features of TDP-43 inclusions is the aberrant phosphorylation of TDP-43 at serines 409/410 (pS409/410). Here, we developed rabbit monoclonal antibodies (mAbs) that specifically detect pS409/410-TDP-43 in multiple model systems and FTD/ALS patient samples. Specifically, we identified three mAbs (26H10, 2E9 and 23A1) from spleen B cell clones that exhibit high specificity and sensitivity to pS409/410-TDP-43 peptides in an ELISA assay. Biochemical analyses revealed that pS409/410 of recombinant TDP-43 and of exogenous 25 kDa TDP-43 C-terminal fragments in cultured HEK293T cells are detected by all three mAbs. Moreover, the mAbs detect pS409/410-positive TDP-43 inclusions in the brains of FTD/ALS patients and mouse models of TDP-43 proteinopathy by immunohistochemistry. Our findings indicate that these mAbs are a valuable resource for investigating TDP-43 pathology both in vitro and in vivo. |
| first_indexed | 2024-04-24T06:03:13Z |
| format | Article |
| id | doaj.art-8a84232f980c4c2ab3c974b7c2363957 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-24T06:03:13Z |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8a84232f980c4c2ab3c974b7c23639572024-04-23T05:31:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01194e029808010.1371/journal.pone.0298080Generation and characterization of monoclonal antibodies against pathologically phosphorylated TDP-43.Paula Castellanos OteroTiffany W ToddWei ShaoCaroline J JonesKexin HuangLillian M DaughrityMei YueUdit ShethTania F GendronMercedes PrudencioBjörn OskarssonDennis W DicksonLeonard PetrucelliYong-Jie ZhangInclusions containing TAR DNA binding protein 43 (TDP-43) are a pathological hallmark of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). One of the disease-specific features of TDP-43 inclusions is the aberrant phosphorylation of TDP-43 at serines 409/410 (pS409/410). Here, we developed rabbit monoclonal antibodies (mAbs) that specifically detect pS409/410-TDP-43 in multiple model systems and FTD/ALS patient samples. Specifically, we identified three mAbs (26H10, 2E9 and 23A1) from spleen B cell clones that exhibit high specificity and sensitivity to pS409/410-TDP-43 peptides in an ELISA assay. Biochemical analyses revealed that pS409/410 of recombinant TDP-43 and of exogenous 25 kDa TDP-43 C-terminal fragments in cultured HEK293T cells are detected by all three mAbs. Moreover, the mAbs detect pS409/410-positive TDP-43 inclusions in the brains of FTD/ALS patients and mouse models of TDP-43 proteinopathy by immunohistochemistry. Our findings indicate that these mAbs are a valuable resource for investigating TDP-43 pathology both in vitro and in vivo.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0298080&type=printable |
| spellingShingle | Paula Castellanos Otero Tiffany W Todd Wei Shao Caroline J Jones Kexin Huang Lillian M Daughrity Mei Yue Udit Sheth Tania F Gendron Mercedes Prudencio Björn Oskarsson Dennis W Dickson Leonard Petrucelli Yong-Jie Zhang Generation and characterization of monoclonal antibodies against pathologically phosphorylated TDP-43. PLoS ONE |
| title | Generation and characterization of monoclonal antibodies against pathologically phosphorylated TDP-43. |
| title_full | Generation and characterization of monoclonal antibodies against pathologically phosphorylated TDP-43. |
| title_fullStr | Generation and characterization of monoclonal antibodies against pathologically phosphorylated TDP-43. |
| title_full_unstemmed | Generation and characterization of monoclonal antibodies against pathologically phosphorylated TDP-43. |
| title_short | Generation and characterization of monoclonal antibodies against pathologically phosphorylated TDP-43. |
| title_sort | generation and characterization of monoclonal antibodies against pathologically phosphorylated tdp 43 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0298080&type=printable |
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